Mechanical ventilation has saved countless lives for those patients suffered with respiratory failures in emergency or under ICU. However, it is a double-edged sword which, at meantime of saving lives, may also cause injuries, such as, ventilator-induced lung injury (or VILI), ventilator-associated pneumonia (or VAP), ventilator-induced diaphragmatic dysfunction (or VIDD) and the like. VIDD refers generally to any injuries induced by mechanical ventilation in the form of diaphragmatic weakness and diaphragm muscle atrophy, resulting in a significant reduction in respiratory capacity and reliance on the breathing machine for breathing. Diaphragmatic function is a key factor to consider in determining whether patients receiving mechanical ventilation can successfully withdraw from the breathing machine. Evidence shows that VIDD is very common in mechanically ventilated patients and causes difficulties in weaning patients. Clinical weaning failure rate is 24%-29%, of which 31% will face a high risk of death. It often necessities extended stays in the intensive care unit, thus extra burdens on healthcare resources of the society and increased medical fees to patients.
As in the field of intensive care unit (referred to as ICU), VILI and VAP caught attentions a long time ago and experts in the field have long been committed to addressing some of the symptoms but the efforts are nonetheless mainly confined to the improvement and adjustment of the operating mode of the ventilator for the purpose of reducing the incidence of VILI. To deal with VAP, the measures are through enhanced care, reduction in infection and timely use of sufficient doses of anti-infection medicines. However, it is only until recent years when attentions are paid to VIDD and therefore there are presently no effective clinical means in preventing and treating VIDD. The usual clinical measure is through medicines, mainly antioxidants such as vitamin E, calpain/cathepsin inhibitors, high-dose corticosteroids, etc. The results are not very certain and some may even be toxic or have no effect at all.
The diaphragm is located between the thoracic cavity and abdominal cavity, being a wide, flat, upward bulging, dome-shaped thin structure of muscle. It is the most important muscle for the breathing function and among all participating muscles its role in the respiratory function accounts for 60%-80%. For respiration of a stationary subject, the diaphragm plays the leading role, and provides the main source of the respiratory pump function. Muscle fibers of the diaphragm can be divided into the following types: Type I is chronic contractile fatigue resistant fibers; Type IIa is rapid contraction fatigue resistant fibers and Type IIb is rapid contraction fatigue fibers. The diaphragm differs from the skeletal muscle in general as it contentiously performs rhythmic contractions with a high contraction ratio, i.e., contraction period/contraction period+relaxation period. If the contractile activity stops, even if only for a few hours, it can cause injuries to the diaphragm and reduce its contracting capability Studies found that lung cancer patients in the process of cancer surgery can suffer injuries in the diaphragm when, due to anesthesia, mechanical ventilation was used for more than 4 hours, as determined from the diaphragm biopsy taken at the same time as the cancer surgery is conducted. In other words, when a human under mechanical ventilation for a period of time, it stops all activities of the respiratory muscles including the diaphragm and causes the diaphragm disuse, resulting in diaphragm muscle fiber damage, muscle atrophy, muscle fiber remodeling, or abnormal excitation-contraction coupling, i.e., VIDD. Furthermore, the degree of injury to the diaphragm depends on the length of the period when mechanical ventilation is used.
Phrenic nerve, originating from the cervical nerves (C3-C5), is responsible for maintaining the respiratory function. It plays an important role in maintaining a normal respiratory function. Normal breathing activity starts with a nerve impulse sent by the central nervous system and transmitted along the phrenic nerve to arrive at the joint between the nerve endplate and the diaphragm, where it activates chemically-gated channel in muscle fiber membranes, causes Na+ influx and K+ efflux, and forms an endplate potential. The endplate potential transmits along the muscle fiber membrane for short distances with an ability of temporal and spacial summation. When the sum of the potential reaches a threshold for muscle fiber contraction, an action potential is generated by which the nerve impulse is turned into an electrical signal, triggering the diaphragmatic contraction to complete inhale action.
Diaphragmatic pacemaker (or diaphragm pacing, DP) is a medical device used to stimulate the phrenic nerve by electrical impulses, causing continuous and rhythmic muscle contractions of the diaphragm which constitute a regular breathing activity mimicking that under physiological conditions.
DP can be the implant type or external type, depending on the location where it is used. The implant type DP, as it requires being implanted in the human body by thoracotomy or VATS electrode implantation, is suitable mainly for long-term ventilation support. Presently, the implant type diaphragmatic pacemaker is difficult to be popularized in China. The external type DP (or external diaphragm pacemaker EDP, which is the type of the DP device relevant to the present invention) is a device which places the pacing electrode on the neck skin to stimulate the most superficial parts of the phrenic nerve beneath the skin. As it avoids surgery and nerve endings being cut-off, it reduces the risk of damaging the phrenic nerve. The external DP has the advantages: simple in structure, convenient to operate, non-invasive, etc., and is a technique for improving the lung ventilation and increasing the activity of the diaphragm. It is mainly used in rehabilitation exercise for patents with chronic obstructive pulmonary disease (i.e., COPD), as short-term supplementary treatments in regular intermittent: 2-3 times in 24 hours, about 30-40 minutes each time. Longer period of electrical stimulation of the phrenic nerve will not help the diaphragmatic function in rehabilitation therapy, and may very easily lead to diaphragmatic fatigue.
The existing external diaphragm pacemaker has not yet, on the level of bio-electrophysiology, attained the capability of intelligently matching with the functional movement state of the diaphragm, and can not be used in conjunction with existing mechanical ventilation methods. Therefore, such diaphragmatic pacemaker has never been used in the treatment of critically ill patients.
The foregoing described process of turning phrenic nerve impulses into electrical signals to trigger contraction of the diaphragm to complete inhale action is referred to as the electrical activity of the diaphragm, or EAdi. EAdi is nerve impulses transmitted to the diaphragm and is the best indicator of neural respiratory events. The existing technology has already achieved the capability of capturing EAdi via electrodes placed in the esophagus and using EAdi to control mechanical ventilation, such as that disclosed in Chinese Patent 200410051035.4 (“Method of starting ventilator using EAdi from an esophageal electrode”). This technology, although having improved man-machine synchronization and reduced man-machine confrontation, cannot however effectively solve the problem of VIDD because it is incapable of improving the situation of diaphragmatic dysfunction.